scholarly journals Inhibitory effect of naphthoquine phosphate on Babesia gibsoni in vitro and Babesia rodhaini in vivo

2022 ◽  
Vol 15 (1) ◽  
Author(s):  
Shengwei Ji ◽  
Mingming Liu ◽  
Eloiza May Galon ◽  
Mohamed Abdo Rizk ◽  
Bumduuren Tuvshintulga ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Treatment Strategies ◽  
Inhibitory Effect ◽  
Significant Inhibition ◽  
New Drugs ◽  
Control Group ◽  
Babesia Gibsoni ◽  
Growth Inhibition Assay

Abstract Background Drug resistance and toxic side effects are major challenges in the treatment of babesiosis. As such, new drugs are needed to combat the emergence of drug resistance in Babesia parasites and to develop alternative treatment strategies. A combination of naphthoquine (NQ) and artemisinin is an antimalarial therapy in pharmaceutical markets. The present study repurposed NQ as a drug for the treatment of babesiosis by evaluating the anti-Babesia activity of naphthoquine phosphate (NQP) alone. Methods An in vitro growth inhibition assay of NQP was tested on Babesia gibsoni cultures using a SYBR Green I-based fluorescence assay. In addition, the in vivo growth inhibitory effect of NQP was evaluated using BALB/c mice infected with Babesia rodhaini. The parasitemia level and hematocrit values were monitored to determine the therapeutic efficacy of NQP and the clinical improvements in NQP-treated mice. Results The half maximal inhibitory concentration of NQP against B. gibsoni in vitro was 3.3 ± 0.5 μM. Oral administration of NQP for 5 consecutive days at a dose of 40 mg/kg of body weight resulted in significant inhibition of B. rodhaini growth in mice as compared with that of the control group. All NQP-treated mice survived, whereas the mice in the control group died between days 6 and 9 post-infection. Conclusion This is the first study to evaluate the anti-Babesia activity of NQP in vitro and in vivo. Our findings suggest that NQP is a promising drug for treating Babesia infections, and drug repurposing may provide new treatment strategies for babesiosis. Graphical Abstract

scholarly journals Inhibitory effect of naphthoquine phosphate against Babesia gibsoni in vitro and Babesia rodhaini in vivo

2021 ◽  
Author(s):  
Shengwei Ji ◽  
Mingming Liu ◽  
Eloiza May Galon ◽  
Mohamed Abdo Rizk ◽  
Bumduuren Tuvshintulga ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Treatment Strategies ◽  
Drug Repurposing ◽  
Significant Inhibition ◽  
Parasite Growth ◽  
New Drugs ◽  
Control Group ◽  
Babesia Gibsoni

Abstract Background: Drug resistance and severe side effects are major challenges in the treatment of babesiosis as they lead to less choices for treatment. Development of new drugs to enrich the treatment strategies and delay the emergence of drug resistance in parasites is still needed. Naphthoquine (NQ) combined with artemisinin treats Plasmodium infection by rapid parasite clearance. The current study repurposed NQ as a babesiosis drug treatment by evaluating the effects of naphthoquine phosphate (NQP) as a single dose treatment for babesiosis. Methods: In vitro anti-Babesia activity of NQP was tested on Babesia gibsoni cultures. The inhibition of parasite growth was verified using a SYBR green I-based fluorescence assay. In vivo efficacy of NQP was evaluated using BALB/c mice infected with Babesia rodhaini. The parasitemia level and hematocrit values were monitored. Results: The half maximal inhibitory concentration of NQP against B. gibsoni in vitro was 3.3 ± 0.5 μM. Oral administration of NQP for 5 successive days at a dose of 40 mg/kg of body weight resulted in significant inhibition on parasite growth compared with the control group. All mice in NQP-treated group survived, whereas the mice in control group died between days 6 and 9 post infection. Conclusion: This is the first study to evaluate the anti-Babesia activity of NQP in vitro and in vivo. The results showed that NQP is a promising drug for babesiosis treatment and drug repurposing may provide new treatment strategies for babesiosis.

IMB-BZ as an Inhibitor Targeting ESX-1 Secretion System to Control Mycobacterial Infection

2021 ◽  
Author(s):  
Pingping Jia ◽  
Yi Zhang ◽  
Jian Xu ◽  
Mei Zhu ◽  
Shize Peng ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterial Infection ◽  
Underlying Mechanism ◽  
Inhibitory Effect ◽  
New Drugs ◽  
Dependent Manner ◽  
High Potency ◽  
Resistance Development

Abstract Background Resistance to anti-tuberculosis (TB) drug is a major issue in TB control, and demands the discovery of new drugs targeting virulence factor ESX-1. Methods We first established a high-throughput screen (HTS) assay for the discovery of ESX-1 secretion inhibitors. The positive hits were then evaluated for the potency of diminishing the survival of virulent mycobacterium and reducing bacterial virulence. We further investigated the probability of inducing drug-resistance and the underlying mechanism using M-PFC. Results A robust HTS assay was developed to identify small molecules that inhibit ESX-1 secretion without impairing bacterial growth in vitro. A hit named IMB-BZ specifically inhibits the secretion of CFP-10 and reduces virulence in an ESX-1-dependent manner, therefore resulting in significant reduction in intracellular and in vivo survival of mycobacteria. Blocking the CFP-10-EccCb1 interaction directly or indirectly underlies the inhibitory effect of IMB-BZ on the secretion of CFP-10. Importantly, our finding shows that the ESX-1 inhibitors pose low risk of drug resistance development by mycobacteria in vitro as compared with traditional anti-TB drug, and exhibit high potency against chronic mycobacterial infection. Conclusion Targeting ESX-1 may lead to the development of novel therapeutics for tuberculosis. IMB-BZ holds the potential for future development into a new anti-TB drug.

scholarly journals Trichostatin A, a potential drug for treatment of animal Babesia infections

2014 ◽  
Vol 11 (2) ◽  
pp. 24-26 ◽  
Author(s):  
T Nyamjargal ◽  
N Oshima ◽  
X Xuan ◽  
I Igarashi ◽  
T Munkhjargal ◽  
...  
Keyword(s):  
Trichostatin A ◽  
Inhibitory Effect ◽  
Babesia Bovis ◽  
Babesia Microti ◽  
Control Group ◽  
Babesia Bigemina ◽  
Theileria Equi ◽  
Babesia Gibsoni

In the present study, we evaluated the inhibitory effect of trichostatin A on the asexual growth of bovine, equine, and canine Babesia parasites in vitro as well as on the in vivo growth of Babesia microti (B.microti) in mice. The growth of Babesia bovis (B.bovis), Babesia bigemina (B.bigemina), Babesia caballi (B.caballi), Theileria equi (T.equi), and Babesia gibsoni (B.gibsoni) species was significantly inhibited (P < 0.05) by very low concentrations of trichostatin A (IC50 values = 2.6, 2.4, 2.3, 2.4, and 2.3 nM, respectively). Furthermore, in B.microti-infected mice, trichostatin A caused significant higher (P < 0.05) inhibition of the growth of B.microti at the dose of 2 mg/kg body weight than that in the control group. These results indicated the trichostatin A might be a chemotherapeutic agent for treatment of babesiosis. DOI: http://dx.doi.org/10.5564/mjas.v11i2.210 Mongolian Journal of Agricultural Sciences Vol.11(2) 2013 pp.24-26

scholarly journals Ajoene, a Sulfur-Rich Molecule from Garlic, Inhibits Genes Controlled by Quorum Sensing

2012 ◽  
Vol 56 (5) ◽  
pp. 2314-2325 ◽  
Author(s):  
Tim Holm Jakobsen ◽  
Maria van Gennip ◽  
Richard Kerry Phipps ◽  
Meenakshi Sundaram Shanmugham ◽  
Louise Dahl Christensen ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Treatment Strategies ◽  
Significant Inhibition ◽  
Control Group ◽  
Content Type ◽  
Multiresistant Bacteria

ABSTRACTIn relation to emerging multiresistant bacteria, development of antimicrobials and new treatment strategies of infections should be expected to become a high-priority research area. Quorum sensing (QS), a communication system used by pathogenic bacteria likePseudomonas aeruginosato synchronize the expression of specific genes involved in pathogenicity, is a possible drug target. Previousin vitroandin vivostudies revealed a significant inhibition ofP. aeruginosaQS by crude garlic extract. By bioassay-guided fractionation of garlic extracts, we determined the primary QS inhibitor present in garlic to be ajoene, a sulfur-containing compound with potential as an antipathogenic drug. By comprehensivein vitroandin vivostudies, the effect of synthetic ajoene towardP. aeruginosawas elucidated. DNA microarray studies of ajoene-treatedP. aeruginosacultures revealed a concentration-dependent attenuation of a few but central QS-controlled virulence factors, including rhamnolipid. Furthermore, ajoene treatment ofin vitrobiofilms demonstrated a clear synergistic, antimicrobial effect with tobramycin on biofilm killing and a cease in lytic necrosis of polymorphonuclear leukocytes. Furthermore, in a mouse model of pulmonary infection, a significant clearing of infectingP. aeruginosawas detected in ajoene-treated mice compared to a nontreated control group. This study adds to the list of examples demonstrating the potential of QS-interfering compounds in the treatment of bacterial infections.

scholarly journals Inhibition of α-Glucosidase, Intestinal Glucose Absorption, and Antidiabetic Properties by Caralluma europaea

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Hayat Ouassou ◽  
Touda Zahidi ◽  
Saliha Bouknana ◽  
Mohamed Bouhrim ◽  
Hassane Mekhfi ◽  
...  
Keyword(s):  
Ethyl Acetate Fraction ◽  
Inhibitory Effect ◽  
Tolerance Test ◽  
Glucose Absorption ◽  
Significant Inhibition ◽  
Oral Glucose ◽  
Glucosidase Activity ◽  
Intestinal Glucose Absorption

Many medicinal plants around the world are used for therapeutic purposes against several diseases, including diabetes mellitus. Due to their composition of natural substances that are effective and do not represent side effects for users, unlike synthetic drugs, in this study, we investigated the inhibitory effect of Caralluma europaea (CE) on α-glucosidase activity in vitro; then the kinetics of the enzyme were studied with increasing concentrations of sucrose in order to determine the inhibition type of the enzyme. In addition, this effect of Caralluma europaea (CE) was confirmed in vivo using rats as an experimental animal model. Among the five fractions of CE, only the ethyl acetate fraction of C. europaea (EACe) induced a significant inhibition of α-glucosidase and its inhibition mode was competitive. The in vivo studies were conducted on mice and rats using glucose and sucrose as a substrate, respectively, to determine the oral glucose tolerance test (OGTT). The results obtained showed that the EACe and the aqueous extract of C. europaea (AECe) have significantly reduced the postprandial hyperglycemia after sucrose and glucose loading in normal and diabetic rats. AECe, also, significantly decreased intestinal glucose absorption, in situ. The results obtained showed that Caralluma europaea has a significant antihyperglycemic activity, which could be due to the inhibition of α-glucosidase activity and enteric absorption of glucose.

Inhibitory Effect of Resveratrol on the Pharmacokinetics of Ticagrelor in Vivo and Vitro

2021 ◽  
Author(s):  
Peng Wang ◽  
Xiao-Xia Hu ◽  
Ying-hui Li ◽  
Nan-Yong Gao ◽  
Guo-quan Chen ◽  
...  
Keyword(s):  
Rat Liver ◽  
Liver Microsomes ◽  
In Vitro Study ◽  
Inhibitory Effect ◽  
Control Group ◽  
Rat Liver Microsomes ◽  
Sprague Dawley ◽  
Group B

This study was to evaluate the effect of resveratrol on the pharmacokinetics of ticagrelor in rats and the metabolism of ticagrelor in human CYP3A4 and liver microsomes. Eighteen Sprague-Dawley rats were randomly divided into three groups: group A (control group), group B (50mg/kg resveratrol), and group C (150mg/kg resveratrol ). After 30 minutes administration of resveratrol, a single dose of ticagrelor (18mg/kg) was administered orally. The vitro experiment was performed to examine the influence of resveratrol on ticagrelor metabolism in CYP3A4*1, human, and rat liver microsomes. Serial biological samples were assayed by validated UHPLC-MS/MS methods. In vivo study, the AUC and Cmax of ticagrelor in group B and C appeared to be significantly higher than the control group, while Vz/F and CLz/F of ticagrelor in group B and C were significantly decreased. In vitro study, resveratrol exhibited an inhibitory effect on CYP3A4*1, human and rat liver microsomes. The IC50 values of resveratrol were 56.75μM，69.07μM and 14.22μM, respectively. Our results indicated that resveratrol had a inhibitory effect on the metabolism of ticagrelor in vitro and vivo. It should be paid more attention to the clinical combination of resveratrol with ticagrelor and ticagrelor plasma concentration should be monitored to avoid the occurrence of adverse reaction.

scholarly journals α-Glucosidase Inhibitory, Anti-Oxidant, and Anti-Hyperglycemic Effects of Euphorbia nivulia–Ham. in STZ-Induced Diabetic Rats

Dose-Response ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 155932582093942
Author(s):  
Muhammad Younus ◽  
Muhammad Mohtasheem ul Hasan ◽  
Khalil Ahmad ◽  
Ali Sharif ◽  
Hafiz Muhammad Asif ◽  
...  
Keyword(s):  
High Performance ◽  
Wistar Rat ◽  
Inhibitory Effect ◽  
Diabetic Rats ◽  
In Vivo Studies ◽  
Control Group ◽  
Control Drug ◽  
Antidiabetic Effects

In this study, we aimed to investigate the antidiabetic effects of Euphorbia nivulia (En), native to Cholistan Desert area of Bahawalpur, Pakistan. First, we performed high-performance liquid chromatography analysis and found that this plant contains ferulic acid, gallic acid, quercetin, benzoic acid, polyphenols, and flavonoids. Then, we performed in vitro and in vivo studies to assess its effects on diabetic Wistar rat model. The experiments were performed and compared with control drug glibenclamide. The 70% hydroalcoholic extract of En exhibited 97.8% in vitro α-glucosidase inhibitory effect at a dose of 1.0 mg/mL. We orally administered the extract of En and control drug to the streptozotocin (STZ)-induced diabetic rats and analyzed its antidiabetic effects. We found that the extract of En with a dose of 500 mg/kg/body weight exhibited significant effect to reduce blood glucose in STZ-induced rats as compared with the control group ( P < .001). Our histological data also showed that the extract significantly improved the histopathology of pancreas. Collectively, both in vitro and in vivo studies revealed that En possesses α-glucosidase inhibitory, antioxidant, and anti-hyperglycemic effect in STZ-induced diabetic rats.

scholarly journals In Vitro and In Vivo Tumor Growth Inhibition by Glutathione Disulfide Liposomes

2017 ◽  
Vol 10 ◽  
pp. 117906441769607 ◽  
Author(s):  
Satya S Sadhu ◽  
Shenggang Wang ◽  
Rakesh Dachineni ◽  
Ranjith Kumar Averineni ◽  
Yang Yang ◽  
...  
Keyword(s):  
Cancer Metastasis ◽  
Cell Function ◽  
Survival Rates ◽  
Significant Inhibition ◽  
Control Group ◽  
Tumor Growth Inhibition ◽  
Tumor Proliferation ◽  
Glutathione Disulfide

Glutathione disulfide (GSSG) is an endogenous peptide and the oxidized form of glutathione. The impacts of GSSG on cell function/dysfunction remain largely unexplored due to a lack of method to specifically increase intracellular GSSG. We recently developed GSSG liposomes that can specifically increase intracellular GSSG. The increase affected 3 of the 4 essential steps (cell detachment, migration, invasion, and adhesion) of cancer metastasis in vitro and, accordingly, produced a significant inhibition of cancer metastasis in vivo. In this investigation, the effect of GSSG liposomes on cancer growth was investigated with B16-F10 and NCI-H226 cells in vitro and with B16-F10 cells in C57BL/6 mice in vivo. Experiments were conducted to elucidate the effect on cell death through promotion of apoptosis and the effect on the cell cycle. The in vivo results with C57BL/6 mice implanted subcutaneously with B16-F10 cells showed that GSSG liposomes retarded tumor proliferation more effectively than that of dacarbazine, a chemotherapeutic drug for the treatment of melanoma. The GSSG liposomes by intravenous injection (GLS IV) and GSSG liposomes by intratumoral injection (GLS IT) showed a tumor proliferation retardation of 85% ± 5.7% and 90% ± 3.9%, respectively, compared with the phosphate-buffered saline (PBS) control group. The median survival rates for mice treated with PBS, blank liposomes, aqueous GSSG, dacarbazine, GLS IV, and GLS IT were 7, 7, 7.5, 7.75, 11.5, and 16.5 days, respectively. The effective antimetastatic and antigrowth activities warrant further investigation of the GSSG liposomes as a potentially effective therapeutic treatment for cancer.

scholarly journals Experimental Application of Sage in Rabbit Husbandry

2008 ◽  
Vol 77 (4) ◽  
pp. 581-588 ◽  
Author(s):  
R. Szabóová ◽  
A. Lauková ◽  
Ľ. Chrastinová ◽  
M. Simonová ◽  
V. Strompfová ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Negative Influence ◽  
Feed Consumption ◽  
Control Group ◽  
Coagulase Negative Staphylococci ◽  
E Coli ◽  
Commercial Feed ◽  
Experimental Group

Salvia spp. belongs to the Labiatae family and is characterized by antimicrobial and antiinflammatory effect. The aim of this study was to test its in vitro and in vivo inhibitory effect against bacteria as well as to find an alternative possibility to use sage in the rabbit ecosystem examining biochemical, zootechnical and inmunological indicators, compared to the commercial feed mixture Xtract. Using the sage extract in in vitro tests, its inhibitory effect was noted. Under in vivo conditions, in the experimental group with sage (EG1), reduction of Pseudomonas-like sp. (p < 0.01) and E. coli (p < 0.01) was noted after 7 days of sage application compared to the control group CG2 (with Robenidin) as well as after 21 days of sage extract application, when the reduction of coagulase-negative staphylococci (p < 0.01) was detected (in comparison with the experimental group-EG2, Xtract group). In the caecum of rabbits from EG1, higher values of lactic, acetic and butyric acids were noted. The values of propionic acid were not influenced. Biochemical indicators were not influenced; however, the values of GSH Px were lower in EG1 compared to EG2. Higher phagocytic activity (18%) was noted in EG1 than in EG2 (13%) after 21 days of additives application. The reduction of Eimeria sp. oocysts was demonstrated in EG1 (sage group) after 7 days of sage application comparing to CG2 (217 OPG to 566 OPG). The animals in both experimental groups achieved higher feed consumption and weight gain, lower mortality compared to both controls. Neither of the additives had a negative influence on the health status and growth performance of rabbits.

scholarly journals Dissecting targeted therapy resistance: Integrating models to quantify environment mediated drug resistance

2017 ◽  
Author(s):  
Noemi Picco ◽  
Erik Sahai ◽  
Philip K. Maini ◽  
Alexander R. A. Anderson
Keyword(s):  
Drug Resistance ◽  
Targeted Therapy ◽  
Targeted Therapies ◽  
Carrying Capacity ◽  
Conflicts Of Interest ◽  
Treatment Strategies ◽  
Model Systems ◽  
Significant Heterogeneity

AbstractDrug resistance is the single most important driver of cancer treatment failure for modern targeted therapies. This resistance may be due to the presence of dormant or aggressive tumor cell phenotypes or to context-driven protection. Non-malignant cells and other factors, constituting the microenvironment in which the tumor grows (the stroma), are now thought to play a crucial role in both therapeutic response and resistance. Specifically, the dialogue between the tumor and stroma has been shown to modulate the response to molecularly targeted therapies, through proliferative and survival signaling. The goal of this work is to investigate interactions between a growing tumor and its surrounding stroma in facilitating the emergence of drug resistance. We use mathematical modeling as a theoretical framework to bridge between experimental models and scales, with the aim of separating the intrinsic and extrinsic components of resistance in BRAF mutated melanoma. The model describes tumor-stroma dynamics both with and without treatment. Calibration of our model, through the integration of experimental data, revealed significant variation across animal replicates in either the intensity of stromal promotion or intrinsic tissue carrying capacity. Furthermore our study highlights the need to account for this variation in the design of treatment strategies. Major Findings. Through the integration of a simple mathematical model with in vitro and in vivo experimental growth dynamics of melanoma cell lines (both with and without drug), we were able to dissect the relative contributions of intrinsic versus environmental resistance. Our study revealed significant heterogeneity in vivo, indicating that there is a diversity of either stromal promotion or tumor carrying capacity under targeted therapy. We believe this variation may be one possible explanation for the heterogeneity observed across patients and within individual patients with multiple metastases. Therefore, quantifying this variation both within in vivo model systems and in individual patients could have a significant impact on the design of future treatment strategies that target both the tumor and stroma. Further, we present guidelines for building more effective and longer lasting therapeutic strategies utilizing our experimentally calibrated model. These strategies explicitly consider the protective nature of the stroma and utilize inhibitors that modulate it.PrecisQuantification of the environmental contribution to drug resistance reveals heterogeneity that significantly alters treatment dynamics that can be exploited for therapeutic gain.Financial SupportPicco and Anderson: US National Cancer Institute grant U01CA151924.Picco: UK Engineering and Physical Sciences Research Council (EPSRC grant number EP/G037280/1).Conflict of Interest DisclosureThe authors declare no potential conflicts of interest.

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